The neuroendocrine system links behavior and experience with hormone secretion. In turn, hormones regulate functions such as reproduction, fluid and mineral intake and balance, metabolism and immune activity. They also help shape the developing brain, affect mood and behavior and contribute to aging and disease. Dr. McEwen studies the cellular and molecular mechanisms underlying the effects of stress and sex hormones on neurogenesis, synaptogenesis and dendritic remodeling in the hippocampal region of the adult and developing brain. The hippocampus is involved in the formation of episodic, spatial and contextual memories and is one of the first brain structures to degenerate in Alzheimer’s disease.

In relation to sex hormone action, the McEwen lab has identified sex hormone receptors in the hippocampus that regulate signaling pathways associated with synapse formation and maturation involving regulation of protein synthesis, neurotransmitter release and cytoskeletal remodeling. These “nongenomic” forms of the classical sex hormone receptors work in concert with the more classical genomic actions of sex hormones on gene expression, and they increase excitatory synapse formation and exert antiseizure and neuroprotective effects in hippocampus and other brain regions.

In relation to stress, the McEwen lab has found that hormone actions on structural plasticity are intertwined with the actions of excitatory amino acid transmitters, kainate receptors, serotonin, GABA, other neurotransmitters and BDNF. Dr. McEwen has found that, in the dentate gyrus, chronic stress reduces neuron number and contributes to cognitive impairment. In the hippocampus, chronic stress causes neurons to undergo remodeling of dendrites. Excitatory amino acids — in particular, NMDA receptors — are important regulators of neuronal remodeling, acting in concert with glucocorticoids. The lab has also shown that the stress-induced remodeling is largely reversed once the stress is removed.

The McEwen lab has recently expanded its scope of study to investigate stress-induced structural remodeling in the amygdala, which is involved in fear and strong emotions, and the prefrontal cortex, which is involved in working memory, decision making and extinction of fear learning. Recent work has found, in humans, an effect of chronic perceived stress on mental flexibility and functional activity in the prefrontal cortex that is analogous to animal studies. In animals, aging leads to loss of the ability to promptly extend dendrites of the prefrontal cortex after cessation of stress.

Work by the neuroimmune-physiology group, headed by Karen Bulloch, has revealed important cell types characteristic of the immune system, namely brain dendritic cells, that are present in the normal, undamaged brain, accumulate in the aging brain and are activated in response to simulated stroke and interferon-γ. The group is working to characterize their functions.

The McEwen laboratory has helped create a new understanding of how the brain changes in adult life and in development, with implications for understanding the impact of stress on the brain and sex differences in human brain function, abnormalities, Alzheimer’s disease, depression, posttraumatic stress disorder and aging.

CAREER

Dr. McEwen received his A.B. in chemistry from Oberlin College in 1959 and his Ph.D. in cell biology from Rockefeller in 1964. He was a United States Public Health Service Postdoctoral Fellow at the Institute of Neurobiology in Göteborg, Sweden, from 1964 to 1965 and an assistant professor in zoology at the University of Minnesota. Dr. McEwen returned to Rockefeller in 1966 as assistant professor. He was appointed associate professor in 1971 and professor and head of laboratory in 1981 and was named Alfred E. Mirsky Professor in 1999.

Dr. McEwen is a past president of the Society for Neuroscience. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences and the Institute of Medicine. He received the 2011 Edward M. Scolnick Prize in Neuroscience and a share of the 2010 Ipsen Foundation Prize in Neuronal Plasticity. In 2009 he received the Gold Medal award from the Society for Biological Psychiatry. In 2005 he received the Pasarow Award in Neuropsychiatry. He is a recipient of the Dale Medal of the British Endocrine Society, and in 2005 he received the Goldman-Rakic Prize for Cognitive Neuroscience from the National Alliance for Research for Schizophrenia and Depression and the Karl Spencer Lashley Award from the American Philosophical Society.